title: Molecular evolution of Na+ channels in teleost fishes.
abstract: Voltage-dependent sodium channels are critical for electrical excitability. Invertebrates possess a single sodium channel gene; two rounds of genome duplication early in vertebrates increased the number to four. Since the teleost-tetrapod split, independent gene duplications in each lineage have further increased the number of sodium channel genes to 10 in tetrapods and 8 in teleosts. Here we review how the occurrence of multiple sodium channel paralogs has influenced the evolutionary history of three groups of fishes: pufferfish, gymnotiform and mormyriform electric fish. Pufferfish (tetraodontidae) produce a neurotoxin, tetrodotoxin, that binds to and blocks the pore of sodium channels. Pufferfish evolved resistance to their own toxins by amino acid substitutions in the pore of their sodium channels. These substitutions had to occur in parallel across multiple paralogs for organismal resistance to evolve. Gymnotiform and mormyriform fishes independently evolved electric organs to generate electricity for communication and object localization. Two sodium channel genes are expressed in muscle in most fishes. In both groups of weakly electric fishes, one gene lost its expression in muscle and became compartmentalized in the evolutionary novel electric organ, which is a muscle derivative. This gene then evolved at elevated rates, whereas the gene that is still expressed in muscle does not show elevated rates of evolution. In the electric organ-expressing gene, amino acid substitutions occur in parts of the channel involved in determining how long the channel will be open or closed. The enhanced rate of sequence evolution of this gene likely underlies the species-level variations in the electric signal.
authors.affiliation: Section of Neurobiology, The University of Texas, Austin, TX, USASection of Integrative Biology, The University of Texas, Austin, TX, USA.
authors.forename: Harold H
authors.initials: HH
authors.lastname: Zakon
authors.affiliation: Section of Neurobiology, The University of Texas, Austin, TX, USASection of Integrative Biology, The University of Texas, Austin, TX, USA.
authors.forename: Manda C
authors.initials: MC
authors.lastname: Jost
authors.affiliation: Section of Neurobiology, The University of Texas, Austin, TX, USASection of Integrative Biology, The University of Texas, Austin, TX, USA.
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Zwickl
authors.affiliation: Section of Neurobiology, The University of Texas, Austin, TX, USASection of Integrative Biology, The University of Texas, Austin, TX, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Section of Neurobiology, The University of Texas, Austin, TX, USASection of Integrative Biology, The University of Texas, Austin, TX, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Hillis
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D004555:Electric Fish / Q000502:physiology*; D004557:Electric Organ / Q000502:physiology; D019143:Evolution, Molecular; D020131:Genes, Duplicate / Q000235:genetics; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D010802:Phylogeny; D016415:Sequence Alignment; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D023721:Tetraodontiformes / Q000502:physiology*; D013779:Tetrodotoxin / Q000633:toxicity
chemical_list: D015222:Sodium Channels; D013779:Tetrodotoxin